17β-estradiol modifies TRPV1 mRNA expression in DRG neurons

Abstract

While it has been demonstrated that women experience greater cancer pain and pain severity than men, the potential role of estrogen in regulating nociception particularly as it relates to tumor pain remains unclear. Current data indicate that estrogens act directly on the nervous system to affect the severity of pain, but the mechanisms underlying this effect are unclear. A major nociceptive mechanism associated with the development of cancer pain is activation of the transient receptor potential vanilloid-1 (TRPV1) channel. TRPV1 is a Ca2+-permeable ionotropic receptor activated by multiple sensory stimuli including heat, acid, and protons. Antagonism of the TRPV1 channel attenuates nociception in a mouse bone cancer pain model. Both estrogen (ER) and TRPV1 receptors are known to be expressed on dorsal root ganglion (DRG) neurons, whose axons transmit pain from the periphery to the spinal cord. This raises the question of whether estrogen can alter TRPV1 receptor expression or function particularly in pain states like cancer pain. The present study was designed to evaluate the effects of estrogen on pain sensitivity and TRPV1 expression in the DRG of male and female C3H mice in a mouse model of bone cancer pain. One goal was to determine whether estrogen modulates nociceptive receptors in the DRG in a manner consistent with its effects on pain sensitivity. This study demonstrated that exposure to 17β-estradiol in gonadectomized males (ORCH+E), but the lack of this same hormone in gonadectomized females (OVX), significantly reduced the mRNA levels of TRPV1 in lumbosacral DRG neurons and this correlated with a reduction in tumor-induced nociception. Our results suggest that modulation of 17β-estradiol causes a down regulation in TRPV1 expression in DRG neurons, which may be associated with a reduction in fibrosarcoma-induced mechanical allodynia in both male female mice.